DESCRIPTION: Mouse hepatitis virus (MHV) is a highly transmissible agent which causes frequent infections in contemporary laboratory mouse colonies. Though most natural MHV infections are self-limiting and clinically inapparent, they significantly impact biomedical research by altering research variables. MHV strains can be segregated based on their initial site of replication into respiratory (R-MHV) and enterotropic (E-MHV) strains. While E-MHV infections are the most common, few studies have been done on their pathogenesis. The recent molecular characterization of two E-MHV strains and improved methods for their in vitro cultivation have allowed us to begin analysis of factors involved in the pathogenesis of E-MHV. The long-term objective of this project is to understand which viral and cellular proteins determine the strict enterotropism of E-MHV strains. The proposed studies will focus on the role of the MHV S protein, through its interaction with cell surface receptors and cell membranes, in determining the unique pathogenicity and limited tissue tropism of E-MHV strains as compared to R-MHV strains. The specific aims of this project are: 1) to characterize virus-receptor interactions for E-MHV as compared to R-MHV strains; 2) to determine the role of the S protein in cell to cell spread of E-MHV as compared to R-MHV strains; and 3) to determine the role of directional entry and release from polarized epithelial cells in MHV pathogenesis.